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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
Neonatal herpes simplex is a HSV infection in an infant. It is a rare but serious condition, usually caused by vertical transmission of HSV-1 or -2) from mother to newborn. During immunodeficiency, herpes simplex can cause unusual lesions in the skin. One of the most striking is the appearance of clean linear erosions in skin creases, with the appearance of a knife cut. Herpetic sycosis is a recurrent or initial herpes simplex infection affecting primarily the hair follicles. Eczema herpeticum is an infection with herpesvirus in patients with chronic atopic dermatitis may result in spread of herpes simples throughout the eczematous areas.
Herpetic keratoconjunctivitis, a primary infection, typically presents as swelling of the conjunctiva and eyelids (blepharoconjunctivitis), accompanied by small white itchy lesions on the surface of the cornea.
Herpetic sycosis is a recurrent or initial herpes simplex infection affecting primarily the hair follicle.
Herpes simplex is divided into two types; HSV-1 causes primarily mouth, throat, face, eye, and central nervous system infections, whereas HSV-2 causes primarily anogenital infections. However, each may cause infections in all areas.
Initial signs of FVR include coughing, sneezing, nasal discharge, conjunctivitis, and sometimes fever (up to 106) and loss of appetite. These usually resolve within four to seven days, but secondary bacterial infections can cause the persistence of clinical signs for weeks. Frontal sinusitis and empyema can also result.
FHV-1 also has a predilection for corneal epithelium, resulting in corneal ulcers, often pinpoint or dendritic in shape. Other ocular signs of FHV-1 infection include conjunctivitis, keratitis, keratoconjunctivitis sicca (decreased tear production), and corneal sequestra. Infection of the nasolacrimal duct can result in chronic epiphora (excess tearing). Ulcerative skin disease can also result from FHV-1 infection. FHV-1 can also cause abortion in pregnant queens, usually at the sixth week of gestation, although this may be due to systemic effects of the infection rather than the virus directly.
In chronic nasal and sinus disease of cats, FHV-1 may play more of an initiating role than an ongoing cause. Infection at an early age may permanently damage nasal and sinus tissue, causing a disruption of ciliary clearance of mucus and bacteria, and predispose these cats to chronic bacterial infections.
A subclinical infection (sometimes called a preinfection) is an infection that, being , is nearly or completely asymptomatic (no signs or symptoms). A subclinically infected person is thus an asymptomatic carrier of a microbe, intestinal parasite, or virus that usually is a pathogen causing illness, at least in some individuals. Many pathogens spread by being silently carried in this way by some of their host population. Such infections occur both in humans and nonhuman animals. An example of an asymptomatic infection is a mild common cold that is not noticed by the infected individual. Since subclinical infections often occur without eventual overt sign, their existence is only identified by microbiological culture or DNA techniques such as polymerase chain reaction.
An individual may only develop signs of an infection after a period of subclinical infection, a duration that is called the incubation period. This is the case, for example, for subclinical sexually transmitted diseases such as AIDS and genital warts. Individuals with such subclinical infections, and those that never develop overt illness, creates a reserve of individuals that can transmit an infectious agent to infect other individuals. Because such cases of infections do not come to clinical attention, health statistics can often fail to measure the true prevalence of an infection in a population, and this prevents the accurate modeling of its infectious transmission.
Herpes infections usually show no symptoms; when symptoms do appear they typically resolve within two weeks. The main symptom of oral infection is inflammation of the mucosa of the cheek and gums—known as acute herpetic gingivostomatitis—which occurs within 5–10 days of infection. Other symptoms may also develop, including headache, nausea, dizziness and painful ulcers—sometimes confused with canker sores—fever, and sore throat.
Primary HSV infection in adolescents frequently manifests as severe pharyngitis with lesions developing on the cheek and gums. Some individuals develop difficulty in swallowing (dysphagia) and swollen lymph nodes (lymphadenopathy). Primary HSV infections in adults often results in pharyngitis similar to that observed in glandular fever (infectious mononucleosis), but gingivostomatitis is less likely.
Recurrent oral infection is more common with HSV-1 infections than with HSV-2. Symptoms typically progress in a series of eight stages:
1. Latent (weeks to months incident-free): The remission period; After initial infection, the viruses move to sensory nerve ganglia (trigeminal ganglion), where they reside as lifelong, latent viruses. Asymptomatic shedding of contagious virus particles can occur during this stage.
2. Prodromal (day 0–1): Symptoms often precede a recurrence. Symptoms typically begin with tingling (itching) and reddening of the skin around the infected site. This stage can last from a few days to a few hours preceding the physical manifestation of an infection and is the best time to start treatment.
3. Inflammation (day 1): Virus begins reproducing and infecting cells at the end of the nerve. The healthy cells react to the invasion with swelling and redness displayed as symptoms of infection.
4. Pre-sore (day 2–3): This stage is defined by the appearance of tiny, hard, inflamed papules and vesicles that may itch and are painfully sensitive to touch. In time, these fluid-filled blisters form a cluster on the lip (labial) tissue, the area between the lip and skin (vermilion border), and can occur on the nose, chin, and cheeks.
5. Open lesion (day 4): This is the most painful and contagious of the stages. All the tiny vesicles break open and merge to create one big, open, weeping ulcer. Fluids are slowly discharged from blood vessels and inflamed tissue. This watery discharge is teeming with active viral particles and is highly contagious. Depending on the severity, one may develop a fever and swollen lymph glands under the jaw.
6. Crusting (day 5–8): A honey/golden crust starts to form from the syrupy exudate. This yellowish or brown crust or scab is not made of active virus but from blood serum containing useful proteins such as immunoglobulins. This appears as the healing process begins. The sore is still painful at this stage, but, more painful, however, is the constant cracking of the scab as one moves or stretches their lips, as in smiling or eating. Virus-filled fluid will still ooze out of the sore through any cracks.
7. Healing (day 9–14): New skin begins to form underneath the scab as the virus retreats into latency. A series of scabs will form over the sore (called Meier Complex), each one smaller than the last. During this phase irritation, itching, and some pain are common.
8. Post-scab (12–14 days): A reddish area may linger at the site of viral infection as the destroyed cells are regenerated. Virus shedding can still occur during this stage.
The recurrent infection is thus often called "herpes simplex labialis". Rare reinfections occur inside the mouth ("intraoral HSV stomatitis") affecting the gums, alveolar ridge, hard palate, and the back of the tongue, possibly accompanied by "herpes labialis".
A lesion caused by herpes simplex can occur in the corner of the mouth and be mistaken for angular cheilitis of another cause. Sometimes termed "angular herpes simplex". A cold sore at the corner of the mouth behaves similarly to elsewhere on the lips. Rather than utilizing antifungal creams, angular herpes simplex is treated in the same way as a cold sore, with topical antiviral drugs.
Feline viral rhinotracheitis (FVR) is an upper respiratory or pulmonary infection of cats caused by "feline herpesvirus 1", of the family "Herpesviridae". It is also commonly referred to as feline influenza, feline coryza, and feline pneumonia but, as these terms describe other very distinct collections of respiratory symptoms, they are misnomers for the condition. Viral respiratory diseases in cats can be serious, especially in catteries and kennels. Causing one-half of the respiratory diseases in cats, FVR is the most important of these diseases and is found worldwide. The other important cause of feline respiratory disease is "feline calicivirus".
FVR is very contagious and can cause severe disease, including death from pneumonia in young kittens. It can cause flat-chested kitten syndrome, but most evidence for this is anecdotal. All members of the "Felidae" family are susceptible to FVR; in fact, FHV-1 has caused a fatal encephalitis in lions in Germany.
The term "labia" means "lip". Herpes labialis does not refer to the labia of the genitals, though the origin of the word is the same. When the viral infection affects both face and mouth, the broader term "orofacial herpes" is used, whereas the term "herpetic stomatitis" is used to specifically describe infection of the mouth; "stomatitis" is derived from the Greek word stoma that means "mouth".
An opportunistic infection is an infection caused by pathogens (bacteria, viruses, fungi, or protozoa) that take advantage of an opportunity not normally available, such as a host with a weakened immune system, an altered microbiota (such as a disrupted gut flora), or breached integumentary barriers. Many of these pathogens do not cause disease in a healthy host that has a normal immune system. However, a compromised immune system, a penetrating injury, or a lack of competition from normal commensals presents an opportunity for the pathogen to infect.
The signs and symptoms of a vertically transmitted infection depend on the individual pathogen. It may cause subtle signs such as a influenza-like illness and may not even be noticed by the mother during the pregnancy. In such cases, the effects may be seen first at birth.
Symptoms of a vertically transmitted infection may include fever and flu like symptoms. The newborn is often small for gestational age. A petechial rash on the skin may be present, with small reddish or purplish spots due to bleeding from capillaries under the skin. An enlarged liver and spleen (hepatosplenomegaly) is common, as is jaundice. However, jaundice is less common in hepatitis B because a newborn's immune system is not developed well enough to mount a response against liver cells, as would normally be the cause of jaundice in an older child or adult. Hearing impairment, eye problems, mental retardation, autism, and death can be caused by vertically transmitted infections. The mother often has a mild infection with few or no symptoms.
The genetic conditions of Aicardi-Goutieres syndrome are possibly present in a similar manner.
Bovine viral diarrhea (BVD) or bovine viral diarrhoea (UK English), and previously referred to as bovine virus diarrhoea (BVD), is a significant economic disease of cattle that is endemic in the majority of countries throughout the world. The causative agent, bovine viral diarrhea virus (BVDV), is a member of the "Pestivirus" genus of the family Flaviviridae.
BVD infection results in a wide variety of clinical signs, due to its immunosuppressive effects, as well as having a direct effect on respiratory disease and fertility. In addition, BVD infection of a susceptible dam during a certain period of gestation can result in the production of a persistently infected (PI) fetus.
PI animals recognise intra-cellular BVD viral particles as ‘self’ and shed virus in large quantities throughout life; they represent the cornerstone of the success of BVD as a disease.
Congenital cytomegalovirus infection refers to a condition where cytomegalovirus is transmitted in the prenatal period.
Human cytomegalovirus is one of the vertically transmitted infections that lead to congenital abnormalities. (Others are: toxoplasmosis, rubella, and herpes simplex. )
BVDV infection has a wide manifestation of clinical signs including fertility issues, milk drop, pyrexia, diarrhoea and fetal infection. Occasionally, a severe acute form of BVD may occur. These outbreaks are characterized by thrombocytopenia with high morbidity and mortality. However, clinical signs are frequently mild and infection insidious, recognised only by BVDV’s immunosuppressive effects perpetuating other circulating infectious diseases (particularly scours and pneumonias).
For infants who are infected by their mothers before birth, two potential adverse scenarios exist:
- Generalized infection may occur in the infant, and can cause complications such as low birth weight, microcephaly, seizures, petechial rash similar to the "blueberry muffin" rash of congenital rubella syndrome, and moderate hepatosplenomegaly (with jaundice). Though severe cases can be fatal, with supportive treatment most infants with CMV disease will survive. However, from 80% to 90% will have complications within the first few years of life that may include hearing loss, vision impairment, and varying degrees of learning disability.
- Another 5% to 10% of infants who are infected but without symptoms at birth will subsequently have varying degrees of hearing and mental or coordination problems. The onset of hearing loss can occur at any point during childhood, although commonly within the first decade. It is progressive and can affect both ears.
These risks appear to be almost exclusively associated with women who previously have not been infected with CMV and who are having their first infection with the virus during pregnancy. There appears to be little risk of CMV-related complications for women who have been infected at least 6 months prior to conception. For this group, which makes up 50% to 80% of the women of child-bearing age, the rate of newborn CMV infection is 1%, and these infants appear to have no significant illness or abnormalities.
The virus can also be transmitted to the infant at delivery from contact with genital secretions or later in infancy through breast milk. However, these infections usually result in little or no clinical illness in the infant.
To summarise, during a pregnancy when a woman who has never had CMV infection becomes infected with CMV, there is a risk that after birth the infant may have CMV-related complications, the most common of which are associated with hearing loss, visual impairment, or diminished mental and motor capabilities. On the other hand, healthy infants and children who acquire CMV after birth have few, if any, symptoms or complications. However, preterm born infants infected with CMV after birth (especially via breastmilk). This can lead to cognitive and motor impairments later in life.
Congenital cytomegalovirus infection can be an important cause of intraventricular hemorrhage and neonatal encephalopathy.
Feline zoonosis are the viral, bacterial, fungal, protozoan, nematode and arthropod infections that can be transmitted to humans from the domesticated cat, "Felis catus". Some of these are diseases are reemerging and newly emerging infections or infestations caused by zoonotic pathogens transmitted by cats. In some instances, the cat can display symptoms of infection (these may differ from the symptoms in humans) and sometimes the cat remains asymptomatic. There can be serious illnesses and clinical manifestations in people who become infected. This is dependent on the immune status and age of the person. Those who live in close association with cats are more prone to these infections. But those that do not keep cats as pets are also able to acquire these infections because of the transmission can be from cat feces and the parasites that leave their bodies.
People can acquire cat-associated infections through bites, scratches or other direct contact of the skin or mucous membranes with the cat. This includes 'kissing' or letting the animal lick the mouth or nose. Mucous membranes are easily infected when the pathogen is in the mouth of the cat. Pathogens can also infect people when there is contact with animal saliva, urine and other body fluids or secretions, When fecal material is unintentionally ingested, infection can occur. Feline zooinosis can be acquired by a person by inhalation of aerosols or droplets coughed up by the cat.
In the United States, forty percent of homes have at least one cat. Some contagious infections such as campylobacteriosis and salmonellosis cause visible symptoms of the disease in cats. Other infections, such as cat scratch disease and toxoplasmosis, have no visible symptoms and are carried by apparently healthy cats.
Aujeszky's disease, usually called pseudorabies in the United States, is a viral disease in swine that has been endemic in most parts of the world. It is caused by "Suid herpesvirus 1" (SuHV1). Aujeszky's disease is considered to be the most economically important viral disease of swine in areas where hog cholera has been eradicated. Other mammals, such as humans, cattle, sheep, goats, cats, dogs, and raccoons, are also susceptible. The disease is usually fatal in these animal species bar humans.
The term "pseudorabies" is found inappropriate by many people, as SuHV1 is a herpesvirus and not related to the rabies virus.
Research on SuHV1 in pigs has pioneered animal disease control with genetically modified vaccines. SuHV1 is now used in model studies of basic processes during lytic herpesvirus infection, and for unravelling molecular mechanisms of herpesvirus neurotropism.
Apart from respiratory involvement, illnesses and presentations of adenovirus include gastroenteritis, conjunctivitis, cystitis, and rash illness. Symptoms of respiratory illness caused by adenovirus infection range from the common cold syndrome to pneumonia, croup, and bronchitis. Patients with compromised immune systems are especially susceptible to severe complications of adenovirus infection. Acute respiratory disease (ARD), first recognized among military recruits during World War II, can be caused by adenovirus infections during conditions of crowding and stress.
Respiratory infection is usually asymptomatic in pigs more than 2 months old, but it can cause abortion, high mortality in piglets, and coughing, sneezing, fever, constipation, depression, seizures, ataxia, circling, and excess salivation in piglets and mature pigs. Mortality in piglets less than one month of age is close to 100%, but it is less than 10% in pigs between one and six months of age. Pregnant swine can reabsorb their litters or deliver mummified, stillborn, or weakened piglets. In cattle (see next section), symptoms include intense itching followed by neurological signs and death. In dogs, symptoms include intense itching, jaw and pharyngeal paralysis, howling, and death Any infected secondary host generally only lives two to three days.
Genital infection appears to have been common in a great part of the 20th century in many European countries in swine herds, where boars from boar centres were used for natural service of sows or gilts. This disease manifestation has always been asymptomatic in affected pigs, and presence of the infection on a farm was detected only because of cases in cattle showing pruritus on the hindquarters (vaginal infection, see below).
In susceptible animals other than swine, infection is usually fatal, and the affected animals most often show intense pruritus in a skin area.
Pruritus in Aujeszky's disease is considered a phantom sensation, and virus has never been found at the site of pruritus.
A vertically transmitted infection is an infection caused by pathogens (such as bacteria and viruses) that uses mother-to-child transmission, that is, transmission directly from the mother to an embryo, fetus, or baby during pregnancy or childbirth. It can occur when the mother gets an infection as an intercurrent disease in pregnancy. Nutritional deficiencies may exacerbate the risks of perinatal infection.
"Pharyngoconjunctival fever" is a specific presentation of adenovirus infection, manifested as:
- high fever that lasts 4–5 days
- pharyngitis (sore throat)
- conjunctivitis (inflamed eyes, usually without pus formation like pink eye)
- enlargement of the lymph nodes of the neck
- headache, malaise, and weakness
- Incubation period of 5–9 days
It usually occurs in the age group 5–18. It is often found in summer camps and during the spring and fall in schools. In Japan, the illness is commonly referred to as "pool fever" as it is often spread via public swimming pools.
Acute toxoplasmosis is often asymptomatic in healthy adults. However, symptoms may manifest and are often influenza-like: swollen lymph nodes, headaches, fever, and fatigue, or muscle aches and pains that last for a month or more. Rarely will a human with a fully functioning immune system develop severe symptoms following infection. People with weakened immune systems are likely to experience headache, confusion, poor coordination, seizures, lung problems that may resemble tuberculosis or Pneumocystis jiroveci pneumonia (a common opportunistic infection that occurs in people with AIDS), or blurred vision caused by severe inflammation of the retina (ocular toxoplasmosis) Young children and immunocompromised people, such as those with HIV/AIDS, those taking certain types of chemotherapy, or those who have recently received an organ transplant, may develop severe toxoplasmosis. This can cause damage to the brain (encephalitis) or the eyes (necrotizing retinochoroiditis). Infants infected via placental transmission may be born with either of these problems, or with nasal malformations, although these complications are rare in newborns. The toxoplasmic trophozoites causing acute toxoplasmosis are referred to as tachyzoites, and are typically found in bodily fluids.
Swollen lymph nodes are commonly found in the neck or under the chin, followed by the armpits and the groin. Swelling may occur at different times after the initial infection, persist, and recur for various times independently of antiparasitic treatment. It is usually found at single sites in adults, but in children, multiple sites may be more common. Enlarged lymph nodes will resolve within one to two months in 60% of cases. However, a quarter of those affected take two to four months to return to normal, and 8% take four to six months. A substantial number (6%) do not return to normal until much later.
Diagnosis of infection is based upon the recovery of the pathogen or pathogens from the typically sterile sites in the mother or the baby. Unfortunately, as many half of pregnant women are asymptomatic with a gonorrhea infection and other sexually transmitted infections. Samples are obtained from urine, blood or cerebrospinal fluid. Diagnosis of infection can also be aided by the use of more nonspecific tests such as determining the total white blood cell count, cytokine levels and other blood tests and signs.
Neonatal infections are infections of the neonate (newborn) during the neonatal period or first four weeks after birth. Neonatal infections may be contracted by transplacental transfer in utero, in the birth canal during delivery (perinatal), or by other means after birth. Some neonatal infections are apparent soon after delivery, while others may develop postpartum within the first week or month. Some infections acquired in the neonatal period do not become apparent until much later such as HIV, hepatitis B and malaria.
There is a higher risk of infection for preterm or low birth weight neonates. Respiratory tract infections contracted by preterm neonates may continue into childhood or possibly adulthood with long-term effects that limit one's ability to engage in normal physical activities, decreasing one's quality of life and increasing health care costs. In some instances, neonatal respiratory tract infections may increase one's susceptibility to future respiratory infections and inflammatory responses related to lung disease.
Antibiotics can be effective treatments for neonatal infections, especially when the pathogen is quickly identified. Instead of relying solely on culturing techniques, pathogen identification has improved substantially with advancing technology; however, neonate mortality has not kept pace and remains 20% to 50%. While preterm neonates are at a particularly high risk, full term and post-term infants can also develop infection. Neonatal infection may also be associated with premature rupture of membranes (breakage of the amniotic sac) which substantially increases the risk of neonatal sepsis by allowing passage for bacteria to enter the womb prior to the birth of the infant. Neonatal infection can be distressing to the family and it initiates concentrated effort to treat it by clinicians.Research to improve treatment of infections and prophylactic treatment of the mother to avoid infections of the infant is ongoing.
Immune reconstitution inflammatory syndrome (IRIS) (also known as immune recovery syndrome) is a condition seen in some cases of AIDS or immunosuppression, in which the immune system begins to recover, but then responds to a previously acquired opportunistic infection with an overwhelming inflammatory response that paradoxically makes the symptoms of infection worse.
IRIS is particularly problematic in cryptococcal meningitis as IRIS is fairly common and can be fatal.
IRIS has been described in immunocompetent hosts who have meningitis caused by "Cryptococcus gattii" and "Cryptococcus neoformans" var. "grubii", environmental fungi which often affect immunocompetent hosts. Several weeks or even months into appropriate treatment, there is a sudden onset deterioration with worsening meningitis symptoms and progression or development of new neurological symptoms.
Magnetic resonance imaging shows increase in the size of brain lesions, and CSF abnormalities (white cell count, protein, glucose) increase. CSF culture is typically sterile, and there is no increase in CSF cryptococcal antigen titer.
The increasing inflammation can cause brain injury or be fatal.
The general mechanism behind IRIS is increased inflammation as the recovering immune system recognizes the antigens of the fungus as immunosuppression is reversed. Cryptococcal IRIS has three phases:
1. before HAART, with a paucity of cerebrospinal fluid (CSF) inflammation and defects in antigen clearance;
2. during initial HAART immune recovery, with pro-inflammatory signaling by antigen-presenting cells without an effector response; and
3. at IRIS, a cytokine storm with a predominant type-1 helper T-cell interferon-gamma response.
Three clinical predictors of cryptococcal-related paradoxical IRIS risk include:
1. lack of initial CSF pleocytosis (i.e. low CSF white blood cell count);
2. elevated C-reactive protein;
3. failure to sterilize the CSF before immune recovery.
IRIS may be the cause of paradoxically worse outcomes for cryptococcal meningitis in immunocompetent compared with immunocompromised hosts, in whom "Cryptococcus neoformans" is the usual pathogen. Treatment with systemic corticosteroids during IRIS may be beneficial in preventing death or progressive neurological deterioration. Steroids given to persons with anti-fungal treatment failure / cryptococcal relapse (in whom CSF cultures are not sterile) can be a fatal iatrogenic error.